Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men A Randomized Clinical Trial

IMPORTANCE Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease. A previous study found an effect of sleep on beta-amyloid (A beta), which is a key protein in Alzheimer disease pathology. OBJECTIVE To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid A beta 42 protein levels in healthy middle-aged men. DESIGN, SETTING, AND PARTICIPANTS The Alzheimer, Wakefulness, and Amyloid Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical trial that took place between June 1, 2012, and October 1, 2012. Participants were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n = 26) recruited from the local population. INTERVENTIONS Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13). MAIN OUTCOMES AND MEASURES Sleep was monitored using continuous polysomnographic recording from 3 PM until 10 AM. Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral A beta 42 concentrations between evening and morning. RESULTS A night of unrestricted sleep led to a 6% decrease in A beta 42 levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation counteracted this decrease. When accounting for the individual trajectories of A beta 42 over time, a difference of 75.8 pg/mL of A beta 42 was shown between the unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04). The individual trajectories of evening and morning A beta 42 concentrations differed between the unrestricted sleep and sleep deprivation groups (P = .04) in contrast to stable A beta 40, tau, and total protein levels. CONCLUSIONS AND RELEVANCE Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in A beta 42. We hypothesize that chronic sleep deprivation increases cerebral A beta 42 levels, which elevates the risk of Alzheimer disease.